A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer

Mark W. Kieran, Christopher D. Turner, Joshua B. Rubin, Susan N. Chi, Mary Ann Zimmerman, Christine Chordas, Giannoula Klement, Andrea Laforme, Amanda Gordon, Amanda Thomas, Donna Neuberg, Timothy Browder, Judah Folkman

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Standard chemotherapeutic drugs, when modified by the frequency and dose of administration, can target angiogenesis. This approach is referred to as antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy. This study evaluated the feasibility of 6 months of metronomic chemotherapy, its toxicity and tolerability, surrogate markers of activity, and preliminary evidence of activity in children with recurrent or progressive cancer. Twenty consecutive children were enrolled and received continuous oral thalidomide and celecoxib with alternating oral etoposide and cyclophosphamide every 21 days for a planned duration of 6 months using antiangiogenic doses of all four drugs. Surrogate markers including bFGF, VEGF, endostatin, and thrombospondin were also evaluated. Therapy was well tolerated in this heavily pretreated population. Toxicities (predominantly reversible bone marrow suppression) responded to dose modifications. Sixty percent of the patients received less than the prescribed 6 months of therapy due to toxicity (one case of deep vein thrombosis), personal choice (1 patient), or disease progression (10 patients). Forty percent of the patients completed the 6 months of therapy, resulting in prolonged or persistent disease-free status. One quarter of all patients continue to be progression free more than 123 weeks from starting therapy. Sixteen percent of patients showed a radiographic partial response. Only elevated thrombospondin-1 levels appeared to correlate with prolonged response. This oral antiangiogenic chemotherapy regimen was well tolerated in this heavily pretreated pediatric population, which showed prolonged or persistent disease-free status, supporting the continued study of antiangiogenic/metronomic chemotherapy in human clinical trials.

Original languageEnglish
Pages (from-to)573-581
Number of pages9
JournalJournal of Pediatric Hematology/Oncology
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2005

Keywords

  • Angiogenesis
  • Antiangiogenesis
  • Clinical trial
  • Metronomic
  • Pediatric
  • Therapy

Fingerprint Dive into the research topics of 'A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer'. Together they form a unique fingerprint.

  • Cite this

    Kieran, M. W., Turner, C. D., Rubin, J. B., Chi, S. N., Zimmerman, M. A., Chordas, C., Klement, G., Laforme, A., Gordon, A., Thomas, A., Neuberg, D., Browder, T., & Folkman, J. (2005). A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. Journal of Pediatric Hematology/Oncology, 27(11), 573-581. https://doi.org/10.1097/01.mph.0000183863.10792.d4